The aim of this research project is the design, synthesis and evaluation of beta-adrenergic antagonists having high selectivity and high affinity for the myocardial beta-adrenoceptors and the potential for being labeled with an appropriate gamma-ray emitting radionuclide. The biologic characterization of the new derivatives employs myocardial isoproterenol-stimulated adenylate cyclase and radioligand displacement from beta-adrenoceptor containing membrane to demonstrate in vitro potency and affinity. Biodistribution, pharmacokinetic and metabolic studies will be performed in normal animals following i.v. administration of the radiolabeled agent. The chemical identity and purity of the new compounds will be determined by IR, NMR, UV, MS, HPLC and elemental analyses. The ability of the labeled agents to discriminate between normal and pathologically altered tissue will be evaluated in animals with experimentally induced myocardial lesions or infarcts. The data from this study will be examined in order to correlate myocardial uptake and selectivity with particular structural features and biologic parameters. The results will provide the basis for a more rational approach to the preparation of myocardial imaging agents that will benefit both clinicians and patients in the diagnosis and management of coronary artery disease.